This proposal deals with the synthesis of pregnenolone, the precursor to progesterone and its inhibition in vitro and in vivo. The in vitro stdies will involve the purification and characterization of the corpus luteum cytochrome P-450. The interactions at the active site will be studied by equilibrium binding, optic and paramagnetic spectral techniques with radioactive and spin-labeled substrate and inhibitor analogs. Other studies will deal with the target effect of the progesterone molecule including its bindng energies and those of monosubstituted congeners. Appropriate substances of potential pharmacologic significance will be assessed further by bioassay. Finally, the effects of aminoglutethimide, its enantiomers, analogs and certain steroids on the production of estrogen and progesterone and their control mechanisms will be investigated in the human.